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The aim of this study was to ascertain the safety of high-intensity focused ultrasound (HIFU) for high-grade cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) in patients with fertility requirements. This was a prospective one-arm study. Consecutive CIN 2/3 patients diagnosed with histopathology were screened, enrolled and treated from September 2019 to September 2020 in the Affiliated Hospital of North Sichuan Medical College. All patients were treated with a combination of HIFU and antiviral treatment with REBACIN. The scheduled follow-up visits were 1 week, 1 mo, 3 mo, 6 mo and 12 mo after surgery. The primary outcomes included cure and human papillomavirus clearance rates. We screened 287 consecutive CIN 2/3 patients in our hospital, 29 of whom were enrolled and treated in this study. The cure rate reached 82.8% at 7 mo after treatment and 96.6% within 1 y. The HPV-negative rate reached 72.4% (21/29) around 6 mo after treatment, with mild side effects during and after the procedure. Our study suggests that in CIN 2/3 study participants with fertility requirements, HIFU + REBACIN therapy is a safe and effective therapeutic option with a high cure rate, HPV clearance and few side effects.

Cervical cancer is a leading cause of cancer among women. Approximately 350,000 women die from cervical needlessly from cancer each year, and 85% of the global burden occurs in low- and middle-income countries (LMICs). Disparities in the incidence and mortality between LMICs and industrialized countries can be attributed to differences in access to human papillomavirus (HPV) vaccination and cervical cancer screening and treatment. The World Health Organization (WHO) is leading a renewed international effort to reduce the global burden of cervical cancer. In this article, we discuss recommendations for HPV vaccination, primary HPV screening, and treatment of precancerous lesions.

Cervical cancer (CC) is the second most common malignancy among women. GEPIA demonstrated that MEF2C-AS1 and its nearby gene MEF2C present downregulation in CC tissues. We attempted to clarify molecular mechanism between MEF2C-AS1 and MEF2C underlying CC progression. RT-qPCR was used to measure expression levels and subcellular distribution of MEF2C-AS1 and MEF2C in CC cell lines. Gain-of-function assays were conducted to reveal roles of MEF2C-AS1 and MEF2C in CC cell behaviors. Bioinformatics, RNA pull down, and RIP assays were performed to assess association of MEF2C-AS1 or MEF2C with miR-20 b-5p in CC cells. Rescue assays were done to assess regulatory function of the MEF2C-AS1-miR-20 b-5p-MEF2C axis in CC cellular processes. MEF2C-AS1 and its nearby gene MEF2C showed downregulation and had a positive expression correlation in CC tissues. MEF2C-AS1 and MEF2C presented downregulation in CC cells, and they majorly distributed in CC cell cytoplasm. MEF2C-AS1 and MEF2C upregulation repressed CC cell proliferative, migratory, and angiogenic abilities. MEF2C-AS1 competitively bound with miR-20 b-5p to upregulate MEF2C in CC cells. The impacts of MEF2C-AS1 elevation on CC cell proliferative, migratory, and angiogenic capabilities were countervailed by miR-20 b-5p overexpression. The impacts of miR-20 b-5p inhibitor on CC cell proliferative, migratory and angiogenic capabilities were countervailed by MEF2C depletion. To sum up, MEF2C-AS1 and its nearby gene MEF2C present downregulation and serve as tumor suppressors in CC cells. MEF2C-AS1 suppresses CC cell malignancy in vitro through sponging miR-20 b-5p to upregulate MEF2C, which may provide a potential new direction for seeking therapeutic plans of CC.

Human papilloma virus type 16 (HPV16) is the most prevalent etiologic agent associated with cervical cancer, and its early proteins E5, E6 and E7 play important roles in cervical epithelium transformation to cervical intraepithelial neoplasia and even cervical cancer. Hence, these oncoproteins are ideal target antigens for developing immunotherapeutic vaccines against HPV-associated infection and cervical cancer. Currently, multi-epitope vaccines have been a promising strategy for immunotherapy for viral infection or cancers. In this study, the E5aa28-46, E6aa37-57 and E7aa26-57 peptides were selected and linked to form a novel multi-epitopes vaccine (E765m), which was inserted into the major immune dominant region (MIR) of hepatitis B virus core antigen (HBc) to construct a HBc-E765m chimeric virus-like particles (cVLPs). The immunogenicity and immunotherapeutic effect of the cVLPs vaccine was evaluated in immunized mice and a tumor-bearing mouse model. The results showed that HBc-E765m cVLPs elicited high E5-, E6- and E7- specific CTL and serum IgG antibody responses, and also relatively high levels of the cytokines IFN-γ, IL-4 and IL-5. More importantly, the cVLPs vaccine significant suppressed tumor growth in mice bearing E5-TC-1 tumors. Our findings provide strong evidence that this novel HBc-E765m cVLPs vaccine could be a candidate vaccine for specific immunotherapy in HPV16-associated cervical intraepithelial neoplasia or cervical cancer.

The purpose of this study was to investigate whether amide proton transfer (APT) imaging and intravoxel incoherent motion (IVIM) imaging can predict tumor response to concurrent chemoradiotherapy (CCRT) in patients with squamous cell carcinoma of the cervix (SCCC).Fifty-nine women (mean age, 54 years ± 10 [standard deviation] years; age range: 32-81 years) with pathologically confirmed SCCC underwent magnetic resonance imaging examination of the pelvis including APT and IVIM before concurrent chemoradiotherapy. They were divided into complete remission (CR) and non-CR groups according to therapeutic effect. APT values and IVIM-derived parameters were measured. Intra- and interobserver agreement for IVIM and APT parameters was assessed using intraclass correlation coefficient (ICC) The independent samples t-test was performed to compare the evaluated parameters between the two groups. Predictive performance for treatment response was evaluated by receiver operator characteristic (ROC) curve analysis.There were 38 and 21 patients in the non-CR and CR groups, respectively. Excellent interobserver and intraobserver agreement were obtained for all IVIM and APT parameters, with ICCs ranging from 0.844 to 0.962. Perfusion fraction (f) and APT values were lower in the CR group compared with the non-CR group (both P0.05). The combination of f and APT values showed good diagnostic performances in predicting response to concurrent chemoradiotherapy, with an area under the ROC curve of 0.852 (95% CI: 0.744-0.961), 79% sensitivity (95% CI: 63-90%), 90% specificity (95% CI: 70-99%) and 83% accuracy (95% CI: 71-92%).APT and IVIM imaging may serve as noninvasive tools for predicting response to concurrent chemoradiotherapy in patients with SCCC.

The persistent infection of high-risk Human papillomavirus (HR-HPV) induced cervical cancer remains a challenge in women worldwide including India. Recent advances in cancer research have paved the way for advanced cancer treatment modalities including immunotherapy by manipulating the function or number of cytotoxic T cells. It is well established that anaphylatoxins like C3a and C5a of complement system influence tumor growth by evading apoptosis leading to progression of cancer. The role of the complement system, particularly the complement regulatory proteins (CRPs) which are important determinants of immune response play a crucial role in carcinogenesis. In a tumor microenvironment (TME) assisted suppression of immune effector cells may be achieved through CRPs. However, recent advances in pharmacogenomics including drug designing and combination of these approaches have provided a holistic understanding of signaling pathways and their crosstalk, to regulate cellular communications.This review describes the role of complement system; particularly CRPs in HPV induced cervical carcinogenesis which may be used for designing anti- HPV or cervical cancer therapeutics.

Human papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent).1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20-26, 27-35, or 36-45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference -10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio 0.5.Among the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded -10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths.This study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.

BACKGROUND: Despite the high burden of cervical cancer, access to preventive measures remains low in India. A single-dose immunisation schedule could facilitate the scale-up of human papillomavirus (HPV) vaccination, contributing to global elimination of cervical cancer. We projected the effect of single-dose quadrivalent HPV vaccination in India in comparison with no vaccination or to a two-dose schedule.METHODS: In this modelling study, we adapted an HPV transmission model (EpiMetHeos) to Indian data on sexual behaviour (from the Demographic and Health Survey and the Indian National AIDS Control Organisation), HPV prevalence data (from two local surveys, from the states of Tamil Nadu and West Bengal), and cervical cancer incidence data (from Cancer Incidence in Five Continents for the period 2008-12 [volume XI], and the Indian National Centre for Disease Informatics and Research for the period 2012-16). Using the model, we projected the nationwide and state-specific effect of HPV vaccination on HPV prevalence and cervical cancer incidence, and lifetime risk of cervical cancer, for 100 years after the introduction of vaccination or in the first 50 vaccinated birth cohorts. Projections were derived under a two-dose vaccination scenario assuming life-long protection and under a single-dose vaccination scenario with protection duration assumptions derived from International Agency for Research on Cancer (IARC) India vaccine trial data, in combination with different vaccination coverages and catch-up vaccination age ranges. We used two thresholds to define cervical cancer elimination: an age-standardised incidence rate of less than 4 cases per 100 000 woman-years, and standardised lifetime risk of less than 250 cases per 100 000 women born.FINDINGS: Assuming vaccination in girls aged 10 years, with 90% coverage, and life-long protection by two-dose or single-dose schedule, HPV vaccination could reduce the prevalence of HPV16 and HPV18 infection by 97% (80% UI 96-99) in 50 years, and the lifetime risk of cervical cancer by 71-78% from 1067 cases per 100 000 women born under a no vaccination scenario to 311 (80% UI 284-339) cases per 100 000 women born in the short term and 233 (219-252) cases per 100 000 women born in the long term in vaccinated cohorts. Under this scenario, we projected that the age-standardised incidence rate threshold for elimination could be met across India (range across Indian states: 1·6 cases [80% UI 1·5-1·7] to 4·0 cases [3·8-4·4] per 100 000 woman-years), while the complementary threshold based on standardised lifetime risk was attainable in 17 (68%) of 25 states, but not nationwide (range across Indian states: 207 cases [80% UI 194-223] to 477 cases [447-514] per 100 000 women born). Under the considered assumptions of waning vaccine protection, single-dose vaccination was projected to have a 21-100% higher per-dose efficiency than two-dose vaccination. Single-dose vaccination with catch-up for girls and women aged 11-20 years was more impactful than two-dose vaccination without catch-up, with reduction of 39-65% versus 38% in lifetime risk of cervical cancer across the ten catch-up birth cohorts and the first ten routine vaccination birth cohorts.INTERPRETATION: Our evidence-based projections suggest that scaling up cervical cancer prevention through single-dose HPV vaccination could substantially reduce cervical cancer burden in India.FUNDING: The Bill & Melinda Gates Foundation.

Intensity-modulated radiotherapy (IMRT) has been used to reduce dose to bone marrow (BM) irradiation during pelvic conformal radiotherapy by contouring bone marrow and sparing it during radiotherapy planning. The present study was done to compare CTMRI for contouring bone marrow to spare functional bone marrow for Intensity-modulated radiotherapy (IMRT) in carcinoma cervix and to assess its effect on functional outcome.This prospective, observational study included newly diagnosed carcinoma cervix patients treated by radical chemoradiation. Patients were distributed in two arms i.e. CT arm and MRI for contouring bone marrow. Regions taken into consideration for bone marrow volumes contouring were 4th and 5th Lumbar vertebrae, whole pelvis and proximal femur upto lesser trochanter. In CT arm bone marrow regions were contoured using freehand method with window adjusted to bone range (Window - 2500/ Level - 400) and in MRI arm BM regions on the MR images that had pixel values similar to muscle or IDEAL IQ sequence based on fat fractions present in bone marrow (BM) was used to contour.17 patients in CT arm and 19 patients in MRI arm were included. There was no significant difference between the groups in terms of Bone Marrow Volume (cmDosimetric parameters of bone marrow V10 and V30 were found to be associated with absolute neutrophil and total leucocyte nadir respectively. Haematological toxicity was observed more in MRI arm but more propspective studies are required for further validation.

The female reproductive tract, similar to other mucosal sites, harbors a specific microbiome commonly dominated by Lactobacillus species (spp.), which has an essential role in maintaining health and homeostasis. Increasing evidence shows that genital tract dysbiosis and/or specific bacteria and cytokines might have an active role in the development and/or progression of HPV infection and cervical intra-epithelial neoplasia (CIN) and as a result cervical cancer. Cross-sectional and longitudinal studies reported that Lactobacillus spp. depletion increases with severity of CIN and that this may negatively affect disease regression rates. It is plausible that Lactobacillus deplete microbiome composition may lead to a pro-inflammatory environment that can increase malignant cell proliferation and HPV E6 and E7 oncogene expression. Future longitudinal cohorts and mechanistic experiments on HPV transfected cells models will further permit exploration of the impact of Lactobacillus spp. on HPV infection.

The study aimed to evaluate the knowledge and attitude of Turkish mothers about cervix cancer,HPV infection and vaccination.This cross-sectional study was conducted the mothers with children aged under 18 years who applied pediatric outpatient clinic.Research data were collected using a face-to-face survey includes sociodemographic characteristics of patients and mothers' knowledge level and attitude about the vaccination for HPV and cervical cancer.The rate of mothers who stated that they knew the causes of cervical cancer was 30.3%. Of the 71.5% mothers did not know whether there was a vaccine that protects against cervical cancer.Of the mothers who stated to have heard about the HPV vaccine, 39.2% said that the HPV vaccine is received at 9 years and above, 35.7% said that it could be given to both genders, and 75% knew that the vaccine is not reimbursed. Educational status (p0.001), working as a healthcare worker (p0.001) and the level of income (p0.001), were significantly correlated with the awareness of the causes of cervical cancer in a positive direction. None of the participants vaccinated their child, 91.5% ask for information about HPV and 67.3% stated that they might consider vaccination.The development of vaccines against HPV has significantly changed the approach used in the treatment of cervical cancer. Healthcare professionals have a great responsibility to inform the public about the HPV vaccine.Healthcare providers can use the results of this study to identify parents at risk for vaccine hesitancy and initiate individualized education to promote on-time childhood vaccination.

This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan.A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types.The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year.A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

This study aimed to investigate the prevalence characteristics of human papillomavirus (HPV) infections in 29,508 female cases in Jinshan District, Shanghai.The current research represents a retrospective study that included 29,508 women who received cervical screening in the Jinshan Branch of Shanghai Sixth People's Hospital from 2010 to 2020. The overall prevalence, distribution types, age-specific prevalence and annual trends were analysed.The overall HPV infection rate among the patients was 21.97%. They were primarily high-risk HPV (HR-HPV) infections (20.30%) and single HPV infections (15.91%). A general decline in HPV and HR-HPV prevalence was observed with time from 33.52% to 25.45% in 2011 to 21.47% and 20.18% in 2020. The most common HPV genotypes were HPV52, HPV16, HPV58, HPV51, HPV53 and HPV68. The infection rates of HPV genotypes, including HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV42, HPV43, HPV66 and HPV68, showed overall declines across different years. The age-specific prevalence of total HPV and HR-HPV infections formed an approximate U-shaped curve with two peaks, one in the ≥55 age group (29.75%, 28.43%) and the other in the25 age group (22.93%, 20.85%). Both total HPV and HR-HPV infection rates decreased to their lowest in the 25-34-year age groups.The prevalence of HPV infections showed a downward tendency with time. Single HPV genotype infections and HR-HPV infections were predominantly detected. The after prevalent characteristics of HPV can help to guide HPV vaccinations and cervical cancer screenings: 1) non-HPV16/HPV18 H R-HPV genotypes were prevalent; 2) non-vaccine-covered HPV53, HPV51 and HPV68 were also prevalent; 3) women above the age of 55 years had the highest HPV and HR-HPV infection rates.

Pelvic exenteration, first described in 1948 and subsequently refined, may be offered as a last hope of cure to patients with recurrent or locally advanced pelvic tumours, where radiotherapy is not an option. It is a complex, morbid, ultra-radical procedure involving en-bloc resection of the female reproductive organs, lower urinary tract, and a portion of the rectosigmoid. This article discusses the evolution of and current indications for pelvic exenteration in gynaecologic oncology as well as the reasons for its decline: primary and secondary prevention of cervical cancer (the recurrence of which is the most common indication for exenteration); improvements in treatment of cervical, endometrial, vaginal and vulvar cancer in the primary and recurrent setting; and the advent of novel therapies.

We report the feasibility, experience, and early outcomes of the combined intracavitary and interstitial dedicated applicator using the Kelowna GYN template (Varian, Palo Alto, CA).The Kelowna GYN template is CT compatible and used for the treatment of gynecologic cancers. In cases with patients that have an intact uterus, a modified applicator system using the Kelowna GYN template and a 3D printed adapter piece allows for compatibility with an intrautaerine tandem.We reviewed the treatment course of 23 patients comprising of 86 fractions of HDR treatment. Median D90 for cervical tumors (n = 7) was 82.4 Gy (range 77.7-92.6); for postoperative cervical tumors (n = 2) was 73.9 Gy (range 72.0-5.8); for vaginal tumors (n = 4) was 85.8 Gy (range 79.8-88.1); for recurrent endometrial (n = 10) was 86.9 Gy (range 74.8-103.2). Median EQD2 D2cc for bladder was 72.4 Gy (range 47.7-99.4), for rectum was 61.2 Gy (range 52.4-80.6), and for sigmoid colon of 50.5 Gy (44.3-66.9). At a median follow-up of 12 months, 2 patients had a local recurrence. Two patients had distant recurrence: one with carcinomatosis at 6 months, and one with pulmonary metastases at 3 months. No patients had late grade three toxicities.Our single institutional experience supports the use of the Kelowna template as a robust system as a combined IC-IS applicator resulting in versatile and reproducible implants for a variety of gynecologic malignancies.

To characterize HPV genotype distribution in HSIL and ICC- biopsies, of WLWH, in Europe, as compared to HIV-negative women.Cohort- and nested -case control study.We characterized HPV genotype distribution by performing PCR on HSIL and ICC biopsies from WLWH (n = 170); 85 cases were compared to 85 HIV-negative matched controls. The proportion of patients that might be protected by HPV vaccines was estimated.Among WLWH (median age 36 years-old, median duration of HIV infection 70,5 months, 79% under cART): the most frequently detected HPV were HPV16 (30%), HPV35 (16%), HPV58 (14,7%), HPV31 (13,5%), and HPV52 (11,7%). HPV16 was less frequently found in WLWH, originating from Central Africa (20,5%) compared to other African regions (35,5%) (p = 0,05) or world regions (38,8%) (p = 0,007). Multiple versus single high-risk HPV infections were associated with younger age (≤35 years)(odds ratio (OR) 2,65 (95%IC: 1,3-5,2,p = 0,002), lymphocyte CD4 count 350 cells / µL (OR 2,7 (95%IC: 2-8,5; p = 0,005), use of cART for 18 month OR 2,2 (95%IC: 1,1-4,5),p = 0,04) or a cumulative time with undetectable HIV viral load of less than 12 months (OR 4,2 (95%IC: 2-8.5,p = 0,001). HPV 31, 33 and 35 were more frequently detected in samples from WLWH than in HIV-negative controls (p 0,05). The 9-valent vaccine would increase HPV protection, in HIV-positive and negative women (p 0,001).WLWH are more frequently infected with high-risk HPV other than 16 and 18 than HIV-negative ones. The use of 9-valent vaccine may prevent HSIL or ICC in up to 85% of the women. Adding HPV 35 to the HPV vaccine panel, might improve vaccine effectiveness in WLWH.

Collating evidence on the impact of highly active antiretroviral therapy (HAART) on the outcome of cervical lesions or human papillomavirus (HPV) infection among women living with HIV (WLHIV) is essential to inform cervical cancer prevention in this vulnerable group.We performed a systematic review and meta-analysis of cohort studies that were conducted between January 1, 1996 and January 31, 2022 and reported on the association of HAART with any of the outcomes: incidence, progression, or regression of cervical lesions or acquisition or clearance of HPV infection in WLHIV. Random-effect analysis was used for summary statistics and heterogeneity was assessed through IAmong 11 studies, the summary estimate of incident cervical lesions was lower in WLHIV on HAART (0.81, 95% CI 0.60-1.08). HAART was associated with lower risk of cervical lesion progression (0.76, 95% CI 0.64-0.92, IThis review provides evidence that HAART assists in reducing the incidence and progression of cervical lesions and enhancing their regression in women living with HIV. Hence, the HAART regime should be recommended to all WLHIV with advice for adherence to allow for early immune reconstitution.

In image-guided adaptive brachytherapy (IGABT) a quantitative evaluation of the dosimetric changes between fractions due to anatomical variations, can be implemented via rigid registration of images from subsequent fractions based on the applicator as a reference structure. With available treatment planning systems (TPS), this is a manual and time-consuming process. The aim of this retrospective study was to automate this process. A neural network (NN) was trained to predict the applicator structure from MR images. The resulting segmentation was used to automatically register MR-volumes.DICOM images and plans of 56 patients treated for cervical cancer with high dose-rate (HDR) brachytherapy were used in the study. A 2D and a 3D NN were trained to segment applicator structures on clinical T2-weighted MRI datasets. Different rigid registration algorithms were investigated and compared. To evaluate a fully automatic registration workflow, the NN-predicted applicator segmentations (AS) were used for rigid image registration with the best performing algorithm. The DICE coefficient and mean distance error between dwell positions (MDE) were used to evaluate segmentation and registration performance.The mean DICE coefficient for the predicted AS was 0.70 ± 0.07 and 0.58 ± 0.04 for the 3D NN and 2D NN, respectively. Registration algorithms achieved MDE errors from 8.1 ± 3.7 mm (worst) to 0.7 ± 0.5 mm (best), using ground-truth AS. Using the predicted AS from the 3D NN together with the best registration algorithm, an MDE of 2.7 ± 1.4 mm was achieved.Using a combination of deep learning models and state of the art image registration techniques has been demonstrated to be a promising solution for automatic image registration in IGABT. In combination with auto-contouring of organs at risk, the auto-registration workflow from this study could become part of an online-dosimetric interfraction evaluation workflow in the future.

Reclassification of endocervical atypical immature metaplasia (AIM) into reactive changes and neoplastic lesion is often challenging. We aimed to accurately reclassify AIM on hematoxylin and eosin (HE)-stained sections without auxiliary immunohistochemistry (IHC). A total of 133 AIM diagnosed by punch biopsy were reclassified by IHC for p16 and Ki-67 into high-grade squamous intraepithelial lesion (HSIL) or negative for intraepithelial lesion or malignancy or low-grade squamous intraepithelial lesion (NILM/LSIL) as a reference. Nuclear features significantly associated with HSIL on HE-stained sections were extracted by multivariate logistic regression analysis. Propensity score (PS) of HSIL was calculated in each case and cut-off was determined by receiver operation characteristic (ROC) curve analysis. As a result, AIM was reclassified into 104 NILM/LSIL and 29 HSIL by IHC. Compared with reference diagnosis, accuracy of pathologists' subjective diagnosis was 54.9% (kappa coefficient, 0.208). Three nuclear features on HE-stained sections, ie, nuclear enlargement with anisokaryosis, nuclear hyperchromasia, and mitosis, were significantly associated with HSIL. The ROC curve analyses revealed that PS and number of nuclear features were significant predictors of HSIL. Diagnostic accuracy of PS-based diagnosis was 76.7% (kappa, 0.447). When AIM with 2 or more of the 3 nuclear features was diagnosed with HSIL, diagnostic accuracy was 77.4% (kappa, 0.448). Nuclear feature-based diagnosis significantly improved diagnostic accuracy on HE-stained sections compared with subjective diagnosis and may be useful when IHC is not available. However, a considerable proportion of AIM would still remain misdiagnosed and IHC for p16 and Ki-67 should be mandatory for accurate reclassification.

To compare survival outcomes of minimally invasive surgery (MIS) and open surgery for radical hysterectomy (RH) in early cervical cancer patients with histologic subtypes of usual-type adenocarcinoma and adenosquamous carcinoma.From two centers' cervical cancer cohorts, patients with 2009 FIGO stage IB1-IB2 who underwent RH between 2007 and 2020 were retrospectively identified. Patients with usual-type adenocarcinoma and adenosquamous carcinoma were included in the analysis after pathologic review according to the updated World Health Organization Classification of Tumors. Clinicopathologic characteristics and survival outcomes were compared in terms of open surgery or MIS.This study included 161 patients. No significant differences were noted in overall survival (OS; P = 0.241) and disease-free survival (DFS; P = 0.156) between patients with usual-type adenocarcinoma (n = 136) and those with adenosquamous carcinoma (n = 25). MIS RH group (n = 99) had a significantly smaller tumor size (P0.001), lesser pathologic parametrial invasion (P = 0.001), and lesser lymph node metastasis (P0.001) than open RH group (n = 62). MIS and open RH groups showed similar OS (P = 0.201) and 3-year DFS rate (87.9% vs. 75.1%; P = 0.184). In multivariate analysis, worse DFS was not associated with MIS (P = 0.589) but was associated with pathologic parametrial invasion (adjusted HR, 3.41; 95% CI, 1.25-9.29; P = 0.016). Consistent results were observed among patients with usual-type adenocarcinoma; MIS was not associated with worse DFS.Comparable survival outcomes were found for MIS and open RH in early-stage cervical usual-type adenocarcinoma and adenosquamous carcinoma. Although MIS RH was not a poor prognostic factor, pathologic parametrial invasion was significantly associated with worse DFS in cervical usual-type adenocarcinoma and adenosquamous carcinoma.

Chemotherapy; Quality of life; Symptoms Quimioterapia; Calidad de vida; Síntomas Quimioteràpia; Qualitat de vida; Símptomes Background In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. Methods Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1–16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. Results Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77–13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08–12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. Conclusions Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain. This work was supported by Regeneron Pharmaceuticals, Inc., and Sanofi.

Cervical adenocarcinoma (CAC) comprises a heterogeneous group of tumors that are not universally associated with HPV infection. As has been shown in other organs, it is becoming increasingly apparent that HPV status significantly affects the prognosis of adenocarcinoma. We conducted a systematic review and meta-analysis to investigate the infection status of high-risk Human papillomavirus (hrHPV) in CAC and evaluate its impact on the survival of patients.PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to May 1st, 2022. Data on HPV infection status and survival outcomes were evaluated using STATA 16.0.Seventy-one studies with 11,278 participants were included in HPV infection analysis and eight studies with 1099 participants were included in prognosis analysis. The HPV infection rate (including high-risk and low-risk) and hrHPV infection rate in CAC were 75% (95% CI 0.70-0.80, 6978 participants) and 75% (95% CI 0.70-0.81, 4906 participants), respectively. HPV-16 and -18 were the most common HPVs in CAC, with pooled infection rates of 37% (95% CI 0.33-0.41, 7848 participants) and 34% (95% CI 0.30-0.38, 7730 participants), respectively. hrHPV infection was associated with better overall survival (HR 0.23, 95% CI 0.11-0.47, 1013 participants), better disease-free survival (HR 0.18, 95% CI 0.07-0.43, 292 participants), better progression-free survival (HR 0.20, 95% CI 0.08-0.47, 271 participants) and less recurrence (RR 0.30, 95% CI 0.07-0.43, 181 participants).HPV infection rates were high in CAC. HPV-16 and -18 had the highest infection rates in CAC. However, hrHPV infection was associated with better survival and less recurrence. Future studies should clarify the relationship between hrHPV infection and other prognostic factors and make reasonable treatment strategies for CAC with different HPV status.CRD42022319390.

To determine the baseline and cumulative risks of cervical intraepithelial lesion grade 3 (CIN3) and invasive cervical cancer in patients withlt;CIN2 colposcopy findings after a low-grade screening cytology finding (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion [LSIL]).By linking administrative databases, including cytology, pathology, cancer registries, and physician billing history, a population-based cohort study was performed on participants withlt;CIN2 initial colposcopy results after a low-grade antecedent cytology finding, between January 2012 and December 2013. Three and 5-year risks of CIN3 and invasive cervical cancer were generated using Kaplan-Meier survival analysis.Among the 36 887 participants included in the study, CIN3 incidence based on referral cytology were as follows at 3 and 5 years, respectively: normal, 0.7% and 0.9%; ASCUS, 4.31% and 5.6%; and LSIL, 5.9% and 7.2%. Three- and 5-year incidence of invasive cancer were 0% and 0.02% for normal cytology, 0.08% and 0.11% for ASCUS, and 0.04% and 0.07% for LSIL, respectively. Stratifying risk by biopsy result at initial colposcopy, 3- and 5-year CIN3 incidences were 2.85% and 3.81% with a negative biopsy, 7.09% and 8.32% with an LSIL biopsy, and 4.11% and 5.2% when no biopsy was done, respectively. Three- and 5-year incidence of invasive cancer was 0% and 0.05% after a negative biopsy, 0% and 0% after LSIL biopsy, and 0.05% and 0.08% when no biopsy was done, respectively.When initial colposcopy is done after a low-grade screening cytology result andlt;CIN2 is identified, the risk of CIN3 and invasive cancer is low, particularly when biopsies indicate LSIL. Surveillance strategies should balance the likelihood of detecting CIN3 with the potential harms over management with too frequent screening or colposcopic interventions in low-risk patients.

Tumor cells release fragments of their DNA into the circulation, so called cell-free tumor DNA (ctDNA) or liquid biopsy. Here, we analyze if cell-free human papillomavirus DNA (ctHPV DNA) is detectable before, during and after treatment, in patients with cervical cancer or pre-malignant lesions that may develop into cervical cancer, and whether ctHPV DNA levels were correlated to patient or tumor characteristics and outcome. Furthermore, total cell-free DNA load is studied using cfAlbumin DNA as a surrogate marker.18 patients with locally advanced CC (LACC), 15 patients with early stage CC (ESCC) and 21 patients with pre-malignant lesions, all with verified HPV16, 18 or 45-positive lesions, were included. Pre- during- and post-treatment plasma were tested for HPV16, 1845 and total cfDNA load using droplet digital PCR.ctHPV DNA was found in 94.4% and 26.7% of pre-treatment plasma of patients with LACC and ESCC respectively, while all samples from patients with pre-malignant lesions were negative. Higher levels of ctHPV DNA were correlated to higher FIGO2018 stage. Patients with LACC and persistent ctHPV DNA at end-of-treatment had significantly worse progression-free survival (PFS) than patients who had cleared the ctHPV DNA (p = 0.007). Patients with total ctDNA-levels above median in pre-treatment plasma had a worse PFS (p = 0.026), compared to patients with total ctDNA-levels below median.ctHPV DNA is a promising prognostic biomarker in locally advanced cervical cancer that should be studied further for clinical use.

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result ingt;62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.

WHO recommends human papillomavirus (HPV) testing and same-day treatment for cervical screening in low-income and middle-income countries (LMICs); however, few published data exist on the validity of the strategy. We aimed to evaluate the clinical performance, treatment completion rates, adverse events profile, and acceptability of a fully integrated strategy, comprising point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation, for screening of cervical cancer in women in Papua New Guinea.HPV-STAT was a large-scale, prospective, single-arm intervention trial conducted at two clinical sites in Papua New Guinea. Cervical screening clinics with an on-site consultant gynaecologist were selected in consultation with national and provincial health authorities, church health services, and local stakeholders. Eligible participants were women aged 30-59 years attending cervical screening services at the two clinics, who were willing to comply with study procedures and able to provide written informed consent. Women self-collected vaginal specimens for point-of-care GeneXpert testing (Cepheid, Sunnyvale, CA, USA) for oncogenic HPV types. Women testing positive for HPV underwent pelvic examination followed by same-day thermal ablation or referral for gynaecology review. All HPV-positive women and a 15% random sample of HPV-negative women provided a clinician-collected cervical specimen for liquid-based cytology. The primary outcome was clinical performance (ie, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the strategy for the detection of high-grade squamous intraepithelial lesion (HSIL) or worse. This trial is registered with ISRCTN, ISRCTN13476702.Between June 5, 2018, and Jan 6, 2020, we recruited 4285 women, 3638 (84·9%) of whom tested negative for HPV and 647 (15·1%) tested positive for one or more oncogenic HPV type. Sensitivity of the algorithm to detect HSIL or worse was 85·4% (95% CI 81·0-89·6), with specificity 89·6% (88·6-90·6), PPV 35·2% (31·6-39·0), and NPV 98·9% (98·6-99·2). Among HPV-positive women, 602 (93·0%) received same-day thermal ablation and 42 (6·5%) were referred for gynaecology review, 37 (88·1%) of whom attended. Acceptability was high among both HPV-positive and HPV-negative women. Among the 329 HPV-positive women who attended a 3-month follow-up visit, 51 (15·5%) reported mild adverse symptoms that resolved in all cases by the follow-up visit. There were no serious adverse events.We conducted the first real-world evaluation of a fully integrated point-of-care HPV self-collect, test, and treat strategy for same-day cervical screening in a LMIC and found it to be effective, acceptable, and safe when implemented at scale in primary health-care facilities in Papua New Guinea. Our findings support the introduction and scale-up of HPV screening and treatment for the control and elimination of cervical cancer in LMICs, as recommended by WHO.Australian National Health and Medical Research Council.

There are substantial disparities in cancer screening for sexual minorities and gender non-conforming patients. In additional to patients having trauma due to negative experiences with the healthcare system, disparities may be heightened due to heteronormative and cisnormative design of screening programs and electronic medical record systems. Furthermore, there are morphologic challenges specific to certain specimen types from the LGBT + population, such as anal cytology samples, cervical cytology from transgender men taking testosterone, and neovaginal cytology samples. Men who have sex with men are at increased risk for anal cancer compared with the general population. While early detection of anal dysplasia decreases the risk of invasive carcinoma, screening programs are not widespread. Cervical cancer screening may be psychologically and physically challenging for transgender men and non-binary patients. The use of exogenous testosterone therapy causes atrophic changes in cervical cytology samples which mimic high-grade dysplasia. The rate of unsatisfactory samples are also increased in this population. Although HPV driven cancers have been reported in patients with neovaginas, there are currently no guidelines about appropriate screening for transgender women and intersex patients who have neovaginas. Cytopathologists can optimize the health of LGBT + patients in many ways including advocating for inclusive screening guidelines, validating self-collection for HPV and cytology samples, updating requisition forms to better capture the spectrum of gender expression, and recognizing the morphologic changes in cytology samples due to exogenous hormone use.

Early Regression Index (ERIA total of 88 patients affected by LACC (FIGO IB2-IVA) and treated with CRT were enrolled. An MRI protocol consisting in two acquisitions (T2-w and DWI) in two times (before treatment and at mid-therapy) was applied. Gross Tumor Volume (GTV) was delineated and ERIERIThis study identified ERI

To examine whether objective bladder function after robot-assisted radical hysterectomy (RRH) for early-stage cervical cancer is correlated with subjective patient-reported outcomes and quality of life during the first year after RRH.Prospective observational study.Karolinska University Hospital, Sweden.Women with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA2-IB1) between July 2017 and May 2019 were assessed for eligibility.RRH.Subjective bladder function was evaluated with the Female Lower Urinary Tract Symptoms and Urinary Incontinence Quality of Life modules of the International Consultation on Incontinence Questionnaire. Objective urinary function was characterized with urodynamic tests, and the nerves ablated at RRH were quantified by using immunohistochemical staining of biopsies from the resected paracervix, vesicouterine, and sacrouterine ligaments. Twenty-seven women were included for analysis at baseline, 2 weeks, 3 months, and 12 months after surgery. RRH caused hypotonia of the urinary bladder (p.05). Patient-reported outcomes of voiding and filling dysfunction were most significant 2 weeks after surgery (p.05) but for most of the women, bladder function recovered within 3 months. No correlations were found with either subjective or objective urinary function and the number of ablated nerves.For most women, objective and subjective urinary bladder dysfunction recovered within 3 months after RRH. The absence of correlation between functional outcomes and ablated autonomous nerves suggests that other underlying causes play a significant role. Early detection of bladder overextension after RRH is paramount, and the role of postoperative bladder catheterization needs further investigation.

To build radiomics based OS prediction tools for local advanced cervical cancer (LACC) patients treated by concurrent chemoradiotherapy (CCRT) alone or followed by adjuvant chemotherapy (ACT). And, to construct adjuvant chemotherapy decision aid.83 patients treated by ACT following CCRT and 47 patients treated by CCRT were included in the ACT cohort and non-ACT cohort. Radiomics features extracted from primary tumor area of T2-weighted MRI. Two radiomics models were built for ACT and non-ACT cohort in prediction of 3 years overall survival (OS). Elastic Net Regression was applied to the the ACT cohort, meanwhile least absolute shrinkage and selection operator plus support vector machine was applied to the non-ACT cohort. Cox regression models was used in clinical features selection and OS predicting nomograms building.The two radiomics models predicted the 3 years OS of two cohorts. The receiver operator characteristics analysis was used to evaluate the 3 years OS prediction performance of the two radiomics models. The area under the curve of ACT and non-ACT cohort model were 0.832 and 0.879, respectively. Patients were stratified into low-risk group and high-risk group determined by radiomics models and nomograms, respectively. And, the low-risk group patients present significantly increased OS, progression-free survival, local regional control, and metastasis free survival compare with high-risk group (P 0.05). Meanwhile the prognosis prediction performance of radiomics model and nomogram is superior to the prognosis prediction performance of Figo stage.The two radiomics model and the two nomograms is a prognosis predictor of LACC patients treated by CCRT alone or followed by ACT.

Cervical cancer is the fourth most common cancer in women, and its precise detection plays a critical role in disease treatment and prognosis prediction. Fluorodeoxyglucose positron emission tomography and computed tomography, i.e., FDG-PET/CT and PET/CT, have established roles with superior sensitivity and specificity in most cancer imaging applications. However, a typical FDG-PET/CT analysis involves the time-consuming process of interpreting hundreds of images, and the intense image screening work has greatly hindered clinicians. We propose a computer-aided deep learning-based framework to detect cervical cancer using multimodal medical images to increase the efficiency of clinical diagnosis. This framework has three components: image registration, multimodal image fusion, and lesion object detection. Compared to traditional approaches, our adaptive image fusion method fuses multimodal medical images. We discuss the performance of deep learning in each modality, and we conduct extensive experiments to compare the performance of different image fusion methods with some state-of-the-art (SOTA) object-detection deep learning-based methods in images with different modalities. Compared with PET, which has the highest recognition accuracy in single-modality images, the recognition accuracy of our proposed method on multiple object detection models is improved by an average of 6.06%. And compared with the best results of other multimodal fusion methods, our results have an average improvement of 8.9%.

National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan.English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment - Normal, ASCUS, LSIL, HSIL and from histological assessment - CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta-analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596.A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3-19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7-89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9-94·9) for cytological cases of HSIL, 76·9% (52·1-94·7) for histological cases of CIN3/AIS, and 75·7% (68·0-82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1-64·9), for quadrivalent genotypes was 58·6% (52·2-64·9) and for nonavalent genotypes was 71·5% (64·9-77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes.HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan.

OBJECTIVE: To systematically appraise the existing published literature on cervical cancer screening utilization, and associated barriers and facilitators, in Nepal.STUDY DESIGN: Systematic literature review and meta-analysis.METHODS: PubMed/MEDLINE, CINAHL, Scopus, Embase, and, Google Scholar were systematically searched using Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. All quantitative and qualitative studies reporting cervical cancer screening (using the Pap smear test or visual inspection with acetic acid or human papillomavirus test) utilization, barriers, and facilitators for screening were identified. A meta-analysis was performed to estimate Nepal's pooled cervical cancer screening utilization proportion.RESULTS: The search yielded 97 records, of which 17 studies were included. Fifteen studies were quantitative and two were qualitative. Of the 17 studies, six were hospital-based and six were community-based. The pooled cervical cancer screening utilization proportion (using Pap smear test) among Nepalese women was 17% from the studies in the hospital settings, and 16% in the community. Six studies reported barriers to cervical cancer screening, of which four reported embarrassments related to the gynecological examination and a low level of knowledge on cervical cancer. Three (of four) studies reported health personnel, and two studies reported screening services-related facilitators for cervical cancer screening.CONCLUSION: Our review reported that cervical cancer screening utilization (16%) is more than four times lower than the national target (70%) in Nepal. Multiple barriers such as low levels of knowledge and embarrassment are associated with cervical cancer screening utilization. Health personnel's gender, counseling, and privacy of screening services were commonly reported facilitators. These findings could help to inform future research, and policy efforts to increase cervical cancer screening utilization in Nepal.

Understanding real-world treatment patterns and proportions of eligible patients in each line of treatment is imperative to inform future clinical trial designs and multi-line treatment algorithm development.We conducted a retrospective observational cohort study of adult women who received first-line (1 L) therapy for r/mCC between 01 September 2014 and 31 December 2019, using The US Oncology Network electronic health records and chart review data. Patients were followed to 31 December 2020. Patient demographic and clinical characteristics, treatment patterns, and clinical outcomes were assessed descriptively.A total of 262 patients with r/mCC met study inclusion criteria (mean age = 53 years). The majority of patients in 1 L received platinum-based chemotherapy doublet plus bevacizumab (66%) or chemotherapy doublet alone (24%). Nearly half the patients (48%) completing 1 L received 2 L therapy. Among these patients, there was no consistent 2 L treatment of choice. Overall median time to treatment discontinuation was 3.5 months from 1 L treatment initiation, and median overall treatment-free interval was 2.1 months from 1 L discontinuation. Besides elevated serum creatinine, abnormal BMI indicated a directional trend for lower likelihood of receiving 2 L. Other predictors may include no prior bevacizumab, worse ECOG, and earlier disease prevention.50% of the patients who initiated 1 L treatment did not receive 2 L therapy, highlighting the need for novel and effective treatment options. As the treatment landscape continues to evolve, we anticipate that more patients will live longer with more treatment options across multiple lines of therapies in the r/mCC setting.

The U.S. Preventive Services Task Force recommends breast, cervical, and colorectal cancer screening to reduce mortality from these cancers, but screening use has been below national targets. The purpose of this study is to examine the proportion of screening-eligible adults who are up to date with these screenings and how screening use compares with Healthy People 2020 targets.Data from the 2019 National Health Interview Survey were used to examine the percentages of adults up to date with breast cancer screening among women aged 50‒74 years without previous breast cancer, cervical cancer screening among women aged 21‒65 years without previous cervical cancer or hysterectomy, and colorectal cancer screening among adults aged 50‒75 years without previous colorectal cancer. Estimates are presented by sociodemographic characteristics and healthcare access factors. Analyses were conducted in 2021.Percentages of adults up to date were 76.2% (95% CI= 75.0, 77.5) for breast cancer screening, 76.4% (95% CI= 75.2, 77.6) for cervical cancer screening, and 68.3% (95% CI= 67.3, 69.3) for colorectal cancer screening. Although some population subgroups met breast and colorectal cancer screening targets (81.1% and 70.5%, respectively), many did not, and cervical cancer screening was below the target for all examined subgroups. Lower education and income, nonmetropolitan county of residence (which included rural counties), no usual source of care or health insurance coverage, and Medicaid coverage were associated with lower screening test use.Estimated use of breast, cervical, and colorectal cancer screening tests based on the 2019 National Health Interview Survey were below national targets. Continued monitoring may allow for examination of screening trends, inform interventions, and track progress in eliminating disparities.

To identify the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and magnetic resonance imaging (MRI)-based radiomics combined with clinical prognostic factors (CPF) in predicting concurrent chemoradiotherapy (CCRT) sensitivity of locally advanced cervical cancer (LACC).A retrospective analysis of 163 patients (assigned to training or test groups) who underwent conventional MRI and IVIM-DWI before CCRT were divided into sensitive and resistant groups according to their efficacy at 6 months after CCRT. Per-treatment IVIM-DWI parameters (ADC, D, DClinical stage, f value, D value, InverseVariance, SizeZoneNonUniformity, and Minimum were selected to construct prediction model. All parameters except D value showed independent diagnostic value in multivariate Logistic regression analysis and composed prediction model, with AUCs of 0.987 and 0.984 for training and test groups, respectively. The calibration curve (Brier score of 0.042, C-index of 0.987), decision curve and clinical impact curve further demonstrated the reliability and clinical value of prediction model.IVIM-DWI, MRI-based radiomics and CPF showed high clinical value in predicting CCRT sensitivity for LACC with better predictive performance when combined.

Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high efficacy with one dose. We updated a systematic literature review of HPV vaccine effectiveness by number of doses in observational studies.We searched Medline and Embase databases from January 1, 2007, through September 29, 2021. Data were extracted and summarized in a narrative synthesis. We also conducted quality assessments for bias due to selection, information, and confounding.Overall, 35 studies were included; all except one were conducted within the context of a recommended three-dose schedule. Evaluations were in countries that used bivalent HPV vaccine (seven), quadrivalent HPV vaccine (27) or both (one). Nine evaluated effectiveness against HPV infection, ten anogenital warts, and 16 cervical abnormalities. All studies were judged to have moderate or serious risk of bias. The biases rated as serious would likely result in lower effectiveness with fewer doses. Investigators attempted to control for or stratify by potentially important variables, such as age at vaccination. Eight studies evaluated impact of buffer periods (lag time) for case counting and 10 evaluated different intervals between doses for two-dose vaccine recipients. Studies that stratified by vaccination age found higher effectiveness with younger age at vaccination, although differences were not all formally tested. Most studies found highest estimates of effectiveness with three doses; significant effectiveness was found among 28/29 studies that evaluated three doses, 19/29 that evaluated two doses, and 18/30 that evaluated one dose. Some studies that adjusted or stratified analyses by age at vaccination found similar effectiveness with three, two and one doses.Observational studies of HPV vaccine effectiveness have many biases. Studies examining persons vaccinated prior to sexual activity and using methods to reduce sources of bias are needed for valid effectiveness estimates.

Intracavitary cervical brachytherapy (BT) has transitioned from a two-dimensional nonvolumetric (NV) dosimetry system to three-dimensional computed tomography (CT) and/or magnetic resonance imaging (MRI)-based planning techniques. The purpose of this study is to retrospectively evaluate the relative improvements in image-guided planning strategies over time with regards to dosimetry, survival, and toxicity.A single site retrospective review of 95 locally advanced cervical cancer patients treated with concurrent chemoradiation and high dose rate BT from 2009 to 2016 were divided into three BT planning groups: point-A based NV dosimetry using CT imaging (n = 37), CT-based volumetric dosimetry (n = 33), and MRI-based volumetric dosimetry (n = 25). Overall survival (OS), progression free survival (PFS), and pelvic control (PC) at 5 years were plotted using Kaplan-Meier curves. Univariate and multivariate (MVA) cox proportional-hazards models calculated hazard-ratios (HZ). Finally, acute and late grade 3-4 toxicities were compared between the cohorts.Both MRI and CT had significantly less D2cc to bowel (p0.001) and sigmoid (p0.001) compared to NV-based planning. On MVA, age (60 vs. ≥60 years) was significant for worse 5-year OS (HZ: 2.48) and PC (HZ: 5.25). MRI, with NV as the reference, had significantly improved 5-year OS (HZ: 0.26), PFS (HZ: 0.34) and PC (HZ: 0.16). There was no significant difference in grade ≥3 toxicities between the cohorts.CT and MRI-based 3D planning had significantly less D2cc to bowel and sigmoid. MRI-based planning had significant improvement in 5-year OS, PFS, and LC compared to NV on MVA.

Reirradiation (re-RT) is a suitable and potentially curative treatment option for in-field locoregional recurrences in gynecological malignancies. Lack of clear guidelines on prescription, dose-response relationship, and clinical outcomes limits its clinical use. This clinical narrative describes the methodology for integration of deformable image registration (DIR) for cumulative dose assessment in the setting of re-RT for gynecologic malignancies, using the tools available within a commercial treatment planning system.Four patients who received re-RT for locoregional recurrence or second cancer within previously irradiated areas for a gynecologic primary were identified. Patient-specific DIR for deformable dose mapping and accumulation was retrospectively performed using intensity-based algorithm provided by the Varian Medical Systems Velocity AI version 4.1. Cumulative equivalent doses in 2 Gy fractions (EQD2) delivered to overlapping targets and organs at risk were generated and compared with the physically summated doses. For both approaches, brachytherapy (BT) component was physically summated in cases where the BT applicator caused significant anatomic distortion.The mean maximum cumulative overlapping target dose was 119.4 GyDIR-based dose accumulation can be used to guide re-RT planning and can provide clinically relevant information, especially in cases with nodal recurrences. Registration of BT data sets remain challenging and requires an individualized assessment when applying these algorithms to clinical practice.

Although minimally invasive hysterectomy (MIS-H) has been associated with worse survival compared to abdominal hysterectomy (AH) for cervical cancer, only 8% of patients in the LACC trial had microinvasive disease (Stage IA1/IA2). We sought to determine differences in outcome among patients undergoing MIS-H, AH or combined vaginal-laparoscopic hysterectomy (CVLH) for microinvasive cervical cancer.A retrospective cohort study of all patients undergoing hysterectomy (radical and non radical) for FIGO 2018, microinvasive cervical cancer across 10 Canadian centers between 2007 and 2019 was performed. Recurrence free survival (RFS) was estimated using Kaplan Meier Survival analysis. Chi-square and log-rank tests were used to compare outcomes.423 patients with microinvasive cervical cancer were included; 259 (61.2%) Stage IA1 (22/8.5% with LVSI) and 164(38.8%) IA2. The median age was 44 years (range 24-81). The most frequent histology was squamous (59.4%). Surgical approach was: 50.1% MIS-H (robotic or laparoscopic), 35.0% AH and 14.9% CVLH. Overall, 70.9% underwent radical hysterectomy and 76.5% had pelvic lymph node assessment. There were 16 recurrences (MIS-H:4, AH:9, CVLH: 3). No significant difference in 5-year RFS was found (96.7% MIS-H, 93.7% AH, 90.0% CVLH, p = 0.34). In a sub-analysis of patients with IA1 LVSI+/IA2(n = 186), survival results were similar. Further, there was no significant difference in peri-operative complications (p = 0.19). Patients undergoing MIS-H had a shorter median length of stay(0 days vs 3 (AH) vs. 1.5 (CVLH), p0.001), but had more ER visits (16.0% vs 3.6% (AH), 3.5% (CVLH), p = 0.036).In this cohort, including only patients with microinvasive cervical cancer, no difference in recurrence was found by surgical approach. This may be due to the low rate of recurrence making differences hard to detect or due to a true lack of difference. Hence, this patient population may benefit from MIS without compromising oncologic outcomes.

This study aimed to explore the impact of including broader value elements in cost-effectiveness analyses by presenting 2 case studies, one on human papillomavirus (HPV) infection and one on early-stage Hodgkin's lymphoma (ESHL).We identified broader value elements (eg, patient and caregiver time, spillover health effects, productivity) from the Second Panel's Impact Inventory and the ISPOR Special Task Force's value flower. We then evaluated the cost-effectiveness of HPV vaccination versus no vaccination (case 1) and combined modality therapy (CMT) versus chemotherapy alone for treatment of adult ESHL (case 2) using published simulation models. For each case study, we compared incremental cost-effectiveness ratios considering health sector impacts only (the "base-case" scenario) with incremental cost-effectiveness ratios incorporating broader value elements.For vaccination of US girls against HPV before sexual debut versus no vaccination, the base-case result was $38 334 per disability-adjusted life-year averted. Including each broader value element made cost-effectiveness progressively more favorable, with HPV vaccination becoming cost-saving (ie, reducing costs and averting more disability-adjusted life-years) when the analysis incorporated productivity costs. For CMT versus chemotherapy alone in patients with ESHL, the base-case result indicated that CMT was cost-saving. Including all elements made this treatment's net monetary benefits (the sum of its averted resource costs and the net value of its health impacts) less favorable, even as the contribution from CMT's near-term health benefits grew.Including broader value elements can substantially influence cost-effectiveness ratios, although the direction and the magnitude of their impact can differ across interventions and disease context.

Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain.In this retrospective cohort study, girls in BIFAP aged 9-18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis.Out of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79-1.76] for exposed (1.25 [0.77-2.04] for bi- and 1.15 [0.76-1.76] for quadri-valent vaccines) and 1.26 [0.74-2.14] for post-exposed periods. HR was 1.50 [0.87-2.59] for the 1We did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1

FIGO stage IVA cervical cancer is a unique diagnosis that conveys a poor prognosis. Despite the use of PET/CT for staging, concurrent chemotherapy, and image-guided brachytherapy, overall survival (OS) in these patients is low. Treatment requires aggressive use of radiotherapy and chemotherapy. We report results of a prospective observational cohort study for patients with de novo stage IVA cervical cancer treated at a single institution.Patients with a new diagnosis of stage IVA cervical cancer treated at an academic institution between 1997 and 2020 were prospectively monitored. Staging was retroactively assigned using the 2018 FIGO staging system. All patients had a PET/CT prior to treatment and were treated with definitive intent radiotherapy with or without chemotherapy. The primary outcome of interest was OS. Secondary outcomes were local control, progression-free survival (PFS), and disease-specific survival (DSS).32 patients with de novo stage IVA cervical cancer were treated with definitive intent radiotherapy. Median follow-up time was 4.27 years (1.31-10.35). 22/32 (69%) of patients received brachytherapy as a part of their definitive treatment, and 28/32 (88%) received chemotherapy concurrently with radiotherapy. 14/32 (44%) of patients had no evidence of disease at last follow-up. The 5-year local control, PFS, DFS, and OS estimates were 79%, 49%, 53%, and 48%, respectively. On multivariate analysis, complete metabolic response was associated with a statistically significant improvement in PFS (HR = 0.256, 95% CI = 0.078-0.836, p = 0.024) and OS (HR = 0.273, 95% CI 0.081-0.919).These data demonstrate a robust OS in patients with stage IVA cervical cancer when treated with definitive chemoradiotherapy.

International audience; Local cervical treatment for squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) removes or ablates a cone-shaped or dome-shaped part of the cervix that contains abnormal cells. This Series paper introduces the 2022 terminology for cone dimensions after local conservative treatment for SIL, CIN, or early invasive cervical cancer. The terminology was prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology. Cone length should be tailored to the type of transformation zone. Treatment of SIL or CIN is associated with an increased risk of preterm birth, which escalates with increasing cone length. There is a lack of agreement regarding terms used to report excised specimen dimensions both intraoperatively and in the pathology laboratory. Consensus is needed to make studies addressing effectiveness and safety of SIL or CIN treatment comparable, and to facilitate their use to improve accuracy of antenatal surveillance and management. This Series paper summarises the current terminology through a review of existing literature, describes new terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment, and recommends use of the new terminology that will facilitate communication between clinicians and foster more specific treatment guidelines that balance obstetrical harm against therapeutic effectiveness.

The human papillomavirus (HPV) is responsible for over 90% of all cervical cancer cases. The use of vaginal gels is often indicated for local vaginal drug delivery. Previous studies have shown that Thymus vulgaris essential oil (TEO) exhibits anticancer properties besides antifungal and antibacterial properties. Its activity derives from a specific increase in free radicals and oxidative stress caused in cancer cells. Furthermore, mitoxantrone (MTX), an anthracenedione, and CThe results showed that TEO + CThe formulation TEO + C

Surgery is the mainstay of treatment in the management of early-stage cervical cancer. Until the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, minimally invasive radical hysterectomy was the recommended approach to treat patients with early-stage disease. The results of the LACC trial questioned the adoption of minimally invasive surgery in cervical cancer. In comparison with the open approach, minimally invasive surgery correlated with worse disease-free and cancer-specific survival. Similarly, other retrospective studies highlighted this correlation, thus corroborating the results of the LACC trials. In the present review, we evaluated current evidence and further prospective of the adoption of minimally invasive radical hysterectomy in cervical cancer. Moreover, we sought to assess some unsolved issues regarding the role of minimally invasive surgery in early-stage cervical cancer patients.

Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.

To report on brachytherapy (BT) workflows for image-based treatments of locally advanced cervical cancer (CC) in Canada.Medical Physicists in every Canadian cancer center were contacted and those with a CC-BT program were emailed a 44-item electronic questionnaire surveying workflow patterns including: fractionation schedules, prescription, equipment, imaging, and treatment delivery.Of 47 centers contacted, all 34 who performed CC-BT participated in the survey. Brachytherapy boost, following external beam treatments, was delivered using high-dose-rate (HDR); one center also used pulsed-dose-rate. Intracavitary and/or interstitial treatments were done in 47% centers for 25-80% of their patients. All centers used image-based planning: CT (32%), CT planned with MRI for contouring (47%), MRI (18%), or cone beam CT (3%). For those performing volume-based planning (74%), the contours commonly included Clinical Target Volume (CTV)-High Risk (HR), CTV-Intermediate Risk, rectum, sigmoid, and bladder. The most common HDR dose-fractionation schedule was 7 [4.6 - 10] Gy in 4 [3 - 6] fractions with radiobiological dose prescriptions performed in 62% centers. Medical physics contribution was significant during most activities along the BT treatment pathway in all centers, especially in planning (88%), second checks (68%), and during treatment delivery (88%).Compared to previous surveys, there is an increasing trend in the use of image-based volumetric planning, interstitial procedures, and radiobiological dose prescription. Cervical cancer brachytherapy in Canada is becoming more streamlined with the use of international practice guidelines. Involvement of medical physicists is vital to all stages of CC-BT, including program implementation, routine quality control, dosimetry, and treatment delivery.

Nerve-sparing radical hysterectomy (NSRH) decreases the negative postoperative consequences of radical surgery for cervical cancer, such as bladder evacuation disorders, colorectal motility disorders, and sexual dysfunction. The aim of this study was to prospectively assess the sexuality and quality of life in a group of women who underwent NSRH with lymphadenectomy for cervical cancer.A total of 65 patients with early-stage cervical cancer underwent NSRH between 2014 and 2016. Patient examinations and questionnaire surveys (Female Sexual Function Index questionnaire and European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-CX24) were conducted, before and one year after the surgery.After the exclusion of 19 sexually inactive women and 10 women who received adjuvant anticancer treatment, 36 sexually active patients treated solely with nerve-sparing surgery were eligible for evaluation. The mean age was 47 years. The average preoperative vaginal length was 9.4 cm, whereas the postoperative length was shortened to 7.1 cm. This study showed no negative impact of NSRH on sexual desire, arousal, satisfaction, orgasm, pain, sexual activity, sexual enjoyment, and sexual worry. The worsening of sexual functioning was recorded during the one-year follow-up. The QLQ-C30 questionnaire confirmed postoperative improvement in global health status and role, emotional, and social functioning.Our study showed using standardized questionnaires that NSRH has no negative impact on sexual desire, arousal, satisfaction, orgasm, pain, sexual activity, frequency of sexual intercourse, sexual enjoyment, and sexual worry, while only the worsening of sexual functioning was recorded. Moreover, NSRH did not cause postoperative deterioration in the quality of life parameters.

We implemented magnetic resonance imaging-based image-guided adaptive brachytherapy (IGABT) for the management of cervical cancer at the Northern Centre for Cancer Care in January 2015. The Royal College of Radiologists recommended IGABT as the new standard of care for the management of cervical cancer in the UK in 2009, following earlier publication of recommendations of Groupe European de Curietherapie of the European Society for Radiotherapy and Oncology for three-dimensional magnetic resonance imaging-based IGABT. The purpose of this study was to investigate if the introduction of IGABT in the management of cervical cancer at our institute indeed improved the treatment outcomes with a better toxicity profile as compared with conventional brachytherapy (CBT).A retrospective analysis of 213 patients with International Federation of Gynecology and Obstetrics stage IB-IVA cervical cancer treated with curative radiotherapy ± chemotherapy at the Northern Centre for Cancer Care was carried out for the period January 2010 to December 2019. Patients were categorised into three groups based on their brachytherapy planning process. Fifty-eight patients were treated with CBT, 35 patients were treated with retrospective brachytherapy (RBT) planning and 120 patients were treated with IGABT. Eighty-six per cent received concomitant chemotherapy with cisplatin. Outcome measures were local control rates, overall and progression-free survival, and impact on treatment-related toxicities.The median follow-up was 36, 32 and 25 months for CBT, RBT and IGABT, respectively. Three-year local control achieved was 70.4, 77.8 and 86.9%, respectively. Three-year overall survival was 53.8, 61.1 and 86.2%, respectively. Grade 2 or 3 bladder and bowel toxicity was 8% and 10% in IGABT group versus 20% and 27% in the CBT group.Our analysis indicated that IGABT proved to be very effective in not only improving locoregional control, but also offered quality survivorship to these women, with a significant drop in radiation-related bladder and bowel toxicities.